Joel Kupfer, MDa; Helme Silvet, MDb; Samuel M. Aguayo, MDa
Correspondence: Joel Kupfer (joel.kupfer@va.gov)
aCarl T. Hayden Veterans Affairs Medical Center, Phoenix, Arizona
bVeterans Affairs Loma Linda Healthcare System, California
Author disclosures The authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies.
Background: Lung cancer is the most common cause of cancer mortality, and cigarette smoking is the most significant risk factor. Among smokers at high risk for lung cancer, atherosclerotic cardiovascular disease (ASCVD) also poses a significant risk for morbidity and mortality. Fortunately, there are opportunities of the prevention of ASCVD events during lung cancer screening (LCS).
Observations: Chest low-dose computed tomography (LDCT) scans used for LCS provide information about the absence or severity of coronary artery calcification (CAC), another independent risk factor of ASCVD events. Of note, there are clinically important differences in using CAC scores to guide primary prevention and statin therapy in smokers eligible for LCS compared with those of the general population. This review article focuses on these differences.
Conclusions: We provide recommendations on using CAC scores from LDCT to guide the prevention of ASCVD events in LCS in addition to using cardiac testing and when referral to a cardiovascular specialist should be considered.
Lung cancer is the most common cause of cancer mortality, and cigarette smoking is the most significant risk factor. Several randomized clinical trials have shown that lung cancer screening (LCS) with nonelectrocardiogram (ECG)-gated low-dose computed tomography (LDCT) reduces both lung cancer and all-cause mortality.1,2 Hence, the US Preventive Screening Task Force (USPSTF) recommends annual screening with LDCT in adults aged 50 to 80 years who have a 20-pack-year smoking history and currently smoke or have quit within the past 15 years.3
Smoking is also an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), and LCS clinical trials acknowledge that mortality from ASCVD events exceeds that of lung cancer.4,5 In an analysis of asymptomatic individuals from the Framingham Heart Offspring study who were eligible for LCS, the ASCVD event rate during a median (IQR) follow-up of 11.4 (9.7-12.0) years was 12.6%.6 However, despite the high rate of ASCVD events in this population, primary prevention strategies are consistently underused. In a study of 5495 individuals who underwent LCS with LDCT, only 40% of those eligible for statins had one prescribed, underscoring the missed opportunity for preventing ASCVD events during LCS.7 Yet the interactions for shared decision making and the availability of coronary artery calcification (CAC) scores from the LDCT provide an ideal window for intervening and preventing ASCVD events during LCS.
CAC is a hallmark of atherosclerotic plaque development and is proportional to plaque burden and ASCVD risk.8 Because of the relationship between CAC, subclinical atherosclerosis, and ASCVD risk, there is an opportunity to use CAC detected by LDCT to predict ASCVD risk and guide recommendations for statin treatment in individuals enrolled in LCS. Traditionally, CAC has been visualized by ECG-gated noncontrast CT scans with imaging protocols specifically designed to visualize the coronary arteries, minimize motion artifacts, and reduce signal noise. These scans are specifically done for primary prevention risk assessment and report an Agatston score, a summed measure based on calcified plaque area and maximal density.9 Results are reported as an overall CAC score and an age-, sex-, and race-adjusted percentile of CAC. Currently, a CAC score ≥ 100 or above the 75th percentile for age, sex, and race is considered abnormal.
High-quality evidence supports CAC scores as a strong predictor of ASCVD risk independent of age, sex, race, and other traditional risk factors.10-12 In asymptomatic individuals, a CAC score of 0 is a strong, negative risk factor associated with very low annualized mortality rates and cardiovascular (CV) events, so intermediate-risk individuals can be reclassified to a lower risk group avoiding or delaying statin therapy.13 As a result, current primary prevention guidelines allow for CAC scoring in asymptomatic, intermediate-risk adults where the clinical benefits of statin therapy are uncertain, knowing the CAC score will aid in the clinical decision to delay or initiate statin therapy.
Unlike traditional ECG-gated CAC scoring, LDCT imaging protocols are non–ECG-gated and performed at variable energy and slice thickness to optimize the detection of lung nodules. Early studies suggested that CAC detected by LDCT could be used in lieu of traditional CAC scoring to personalize risk.14,15 Recently, multiple studies have validated the accuracy and reproducibility of LDCT to detect and quantify CAC. In both the NELSON and the National Lung Screening Trial (NLST) LCS trials, higher visual and quantitative measures of CAC were independently and incrementally associated with ASCVD risk.16,17 A subsequent review and meta-analysis of 6 LCS trials confirmed CAC detected by LDCT to be an independent predictor of ASCVD events regardless of the method used to measure CAC.18
There is now consensus that either an Agatston score or a visual estimate of CAC be reported on all noncontrast, noncardiac chest CT scans irrespective of the indication or technique, including LDCT scans for LCS using a uniform reporting system known as the Coronary Artery Calcium Data and Reporting System (CAC-DRS).19 The CAC-DRS simplifies reporting and adds modifiers indicating if the reported score is visual (V) or Agatston (A) and number of vessels involved. For example, CAC-DRS A0 or CAC-DRS V0 would indicate an Agatston score of 0 or a visual score of 0. CAC-DRS A1/N2 would indicate a total Agatston score of 1-99 in 2 coronary arteries. The currently agreed-on CAC-DRS risk groups are listed in the Table, along with their corresponding visual score or Agatston score and anticipated 10-year event rate, irrespective of other risk factors.20
As LCS efforts increase, primary care practitioners will receive LDCT reports that now incorporate an estimation of CAC (visual or quantitative). Thus, it will be increasingly important to know how to interpret and use these scores to guide clinical decisions regarding the initiation of statin therapy, referral for additional testing, and when to seek specialty cardiology care. For instance, does the absence of CAC (CAC = 0) on LDCT predict a low enough risk for statin therapy to be delayed or withdrawn? Does increasing CAC scores on follow-up LDCT in individuals on statin therapy represent treatment failure? When should CAC scores trigger additional testing, such as a stress test or referral to cardiology specialty care?
